Background
Methods
Data sources
Study design
Exposure data
Covariates
Statistical analysis
Statistical analysis for low-dose aspirin use after diagnosis
Statistical analysis for low-dose aspirin use before diagnosis
Results
Patient cohort
Patient characteristics
Characteristics | Total study population | Low-dose aspirin use in year prior to diagnosisa | Low-dose aspirin use after diagnosisb | ||
---|---|---|---|---|---|
User n (%) | Non-user (%) | Ever n (%) | Never (%) | ||
(n = 14,735)
|
(n = 13,433)
|
(n = 3,635)
| |||
Year of diagnosis: 1998–2000 | 2,797 (19) | 459 (12) | 1,850 (19) | 175 (15) | 463 (19) |
2001–2003 | 3,708 (25) | 831 (22) | 2,524 (26) | 280 (24) | 603 (24) |
2004–2006 | 4,025 (27) | 1,175 (30) | 2,603 (27) | 322 (28) | 647 (26) |
2007–2009 | 4,205 (29) | 1,404 (36) | 2,587 (27) | 384 (33) | 761 (31) |
Age at diagnosis: < 50 | 492 (3) | 11 (0) | 410 (4) | 10 (1) | 163 (7) |
50–59 | 1,780 (12) | 171 (4) | 1,425 (15) | 97 (8) | 475 (19) |
60–69 | 3,912 (27) | 916 (24) | 2,660 (28) | 362 (31) | 804 (33) |
70–79 | 5,347 (36) | 1,681 (44) | 3,231 (34) | 478 (31) | 775 (31) |
80–89 | 2,898 (20) | 974 (25) | 1,677 (18) | 199 (17) | 242 (10) |
≥90 | 306 (2) | 116 (3) | 161 (2) | 15 (1) | 15 (1) |
Gender: Males | 8,701 (59) | 1,581 (63) | 6,360 (58) | 748 (64) | 1,357 (55) |
Treatment within 6 months of cancer diagnosis | |||||
Surgeryc | 1,324 (12) | 329 (11) | 895 (12) | 305 (34) | 567 (30) |
Chemotherapy | 3,287 (22) | 709 (18) | 2,324 (24) | 309 (27) | 950 (38) |
Radiotherapy | 4,668 (32) | 1,129 (29) | 3,100 (32) | 389 (34) | 989 (40) |
Histology: Non-small cell | 8,224 (56) | 2,066 (53) | 5,478 (57) | 822 (71) | 1,793 (73) |
Small cell | 1,828 (12) | 458 (12) | 1,218 (13) | 121 (10) | 303 (12) |
Missing | 4,683 (32) | 1,345 (35) | 2,868 (30) | 218 (19) | 378 (15) |
Smoking status prior to cancer diagnosis | |||||
Non-smoker | 1,907 (13) | 543 (14) | 1,188 (12) | 148 (13) | 339 (14) |
Ex-smoker | 5,214 (35) | 1,754 (45) | 3,111 (33) | 541 (47) | 852 (34) |
Current smoker | 5,961 (41) | 1,329 (34) | 4,138 (43) | 393 (34) | 1,042 (42) |
Missing | 1,653 (11) | 243 (6) | 1,127 (12) | 79 (7) | 241 (10) |
Alcohol consumption prior to diagnosis | |||||
Never | 2,311 (16) | 727 (19) | 1,385 (15) | 190 (16) | 342 (14) |
Ever | 9,707 (66) | 2,678 (69) | 6,337 (66) | 841 (72) | 1,712 (69) |
Missing | 2,717 (18) | 464 (12) | 1,842 (19) | 130 (11) | 420 (17) |
BMI (kg/m2) prior to diagnosis: mean (sd) | |||||
Underweight (<18.5) | 735 (5) | 175 (5) | 487 (5) | 38 (3) | 100 (4) |
Normal (18.5 to 25) | 5,325 (36) | 1,379 (36) | 3,543 (37) | 401 (35) | 943 (38) |
Overweight (25–30) | 3,916 (27) | 1,199 (31) | 2,444 (26) | 388 (33) | 695 (28) |
Obese (>30) | 1,702 (12) | 602 (16) | 1,002 (11) | 196 (17) | 287 (12) |
Missing | 3,057 (21) | 514 (13) | 2,088 (22) | 138 (12) | 449 (18) |
Deprivation fifth: 1st (least deprived) | 2,583 (18) | 650 (17) | 1,696 (18) | 206 (18) | 481 (19) |
2nd | 2,822 (19) | 754 (20) | 1,833 (19) | 236 (20) | 451 (18) |
3rd | 2,975 (20) | 778 (20) | 1,954 (20) | 232 (20) | 492 (20) |
4th | 3,235 (22) | 815 (21) | 2,102 (22) | 250 (22) | 556 (23) |
5th (most deprived) | 3,062 (21) | 859 (22) | 1,947 (20) | 233 (20) | 489 (20) |
Missing | 58 (0) | 13 (0) | 32 (0) | 4 (0) | 5 (0) |
Comorbidity prior to cancer diagnosis | |||||
Cerebrovascular disease | 1,.325 (9) | 746 (19) | 498 (5) | 147 (13) | 95 (4) |
Chronic pulmonary disease | 3,619 (25) | 1,054 (27) | 2,341 (25) | 307 (26) | 621 (25) |
Congestive heart disease | 954 (7) | 413 (11) | 483 (5) | 83 (7) | 76 (3) |
Diabetes | 1,552 (11) | 758 (20) | 698 (7) | 194 (17) | 141 (6) |
Myocardial infarction | 1,262 (9) | 866 (22) | 316 (3) | 223 (19) | 67 (3) |
Peptic ulcer disease | 1,087 (7) | 264 (7) | 745 (8) | 65 (6) | 182 (7) |
Peripheral vascular disease | 1,422 (10) | 780 (20) | 576 (6) | 200 (17) | 127 (5) |
Renal disease | 864 (6) | 441 (11) | 397 (4) | 97 (8) | 99 (4) |
Other medication use after diagnosis | |||||
Statin used | 4,801 (33) | 2,103 (54) | 1,193 (13) | 705 (61) | 410 (17) |
Beta-blocker used | 3,823 (26) | 1,143 (30) | 1,005 (11) | 416 (36) | 272 (11) |
Association between low-dose aspirin use after diagnosis and survival
Medication usage after diagnosis | Cancer-specific deaths | All-cause mortality | All patients | Person years | Cancer-specific mortality | All-cause mortality | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted |
P
| Adjusteda |
P
| Unadjusted |
P
| Adjusteda |
P
| |||||||||
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |||||||||
Number of patients
|
[n = 3,635]
|
[n = 2,791]
|
[n = 3,635]
|
[n = 2,791]
| ||||||||||||
Aspirin non-user | 1,609 | 1,855 | 2,474 | 4,481 | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | ||||
Aspirin userb | 638 | 795 | 1,161 | 2,264 | 0.96 | 0.87, 1.05 | 0.36 | 0.96 | 0.85, 1.09 | 0.55 | 1.00 | 0.92, 1.09 | 0.92 | 0.94 | 0.84, 1.05 | 0.28 |
Aspirin non-user | 1,609 | 1,855 | 2,474 | 4,481 | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | ||||
Aspirin user 1 to 11 prescriptionsc | 440 | 521 | 670 | 1,189 | 0.94 | 0.85, 1.04 | 0.25 | 0.95 | 0.83, 1.08 | 0.42 | 0.97 | 0.88, 1.07 | 0.60 | 0.93 | 0.83, 1.05 | 0.24 |
Aspirin user ≥ 12 prescriptionsc | 198 | 274 | 491 | 1,075 | 1.00 | 0.86, 1.17 | 0.96 | 1.01 | 0.84, 1.23 | 0.89 | 1.07 | 0.94, 1.23 | 0.29 | 0.97 | 0.82, 1.14 | 0.69 |
Aspirin non-user | 1,609 | 1,855 | 2,474 | 4,481 | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | ||||
Aspirin user 1–365 tabletsc | 353 | 422 | 541 | 926 | 0.91 | 0.81, 1.02 | 0.12 | 0.92 | 0.80, 1.06 | 0.27 | 0.96 | 0.86, 1.07 | 0.44 | 0.92 | 0.81, 1.05 | 0.21 |
Aspirin user ≥366 tabletsc | 285 | 373 | 620 | 1,338 | 1.03 | 0.90, 1.17 | 0.69 | 1.04 | 0.88, 1.23 | 0.67 | 1.07 | 0.95, 1.20 | 0.28 | 0.97 | 0.84, 1.13 | 0.72 |
Cancer-specific deaths | All patients | Person years | User versus non-user | User versus non-user | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Unadjusted |
P
| Adjusted HRa |
P
| P for interaction | ||||||
HRa | 95 % CI | HRa | 95 % CI | |||||||
Main analysis: Aspirin user versus non-user after diagnosis | 2,247 | 3,635 | 6,745 | 0.96 | 0.87, 1.05 | 0.36 | 0.96 | 0.85, 1.09 | 0.55 | |
Sub group analyses: Aspirin user versus non-user after diagnosis, restricted to: | ||||||||||
Males | 1,312 | 2,105 | 3,750 | 1.00 | 0.89, 1.12 | 0.97 | 1.05 | 0.90, 1.22 | 0.54 | 0.12 |
Females | 935 | 1,530 | 2,995 | 0.87 | 0.75, 1.02 | 0.08 | 0.81 | 0.66, 0.99 | 0.05 | |
Pre-diagnosis aspirin non-usersb | 1,515 | 2,446 | 4,578 | 0.89 | 0.74, 1.07 | 0.21 | 0.91 | 0.73, 1.14 | 0.42 | 0.48 |
Pre-diagnosis aspirin usersb | 554 | 908 | 1,601 | 0.92 | 0.72, 1.16 | 0.47 | 1.02 | 0.77, 1.35 | 0.90 | |
Small cell lung cancer | 328 | 424 | 592 | 0.84 | 0.66, 1.09 | 0.19 | 0.72 | 0.52, 1.01 | 0.05 | 0.03 |
Non-small cell lung cancer | 1,523 | 2,615 | 5,355 | 0.95 | 0.85, 1.06 | 0.35 | 1.00 | 0.86, 1.16 | 0.99 | |
Surgically treated | 305 | 872 | 2,714 | 0.99 | 0.78, 1.27 | 0.96 | 0.95 | 0.71,1.28 | 0.74 | 0.39 |
Non-surgically treated | 820 | 1,708 | 4,216 | 0.94 | 0.80, 1.10 | 0.42 | 0.89 | 0.74, 1.07 | 0.22 | |
Sensitivity analyses: Aspirin user versus non-user after diagnosis | ||||||||||
Increasing lag to 1 year | 2,247 | 3,635 | 6,745 | 0.97 | 0.88, 1.07 | 0.56 | 0.97 | 0.85, 1.10 | 0.60 | |
Excluding patients who died within the first 6 months after diagnosis | 4,440 | 6,158 | 9,101 | 0.96 | 0.90, 1.03 | 0.28 | 0.95 | 0.87–1.04 | 0.30 | |
Additionally adjusting for smoking prior to diagnosis | 2037 | 3,315 | 6,074 | 0.95 | 0.86, 1.04 | 0.28 | 0.95 | 0.84, 1.08 | 0.41 | |
Additionally adjusting for BMI prior to diagnosis | 1,849 | 3,048 | 5,640 | 0.93 | 0.84, 1.03 | 0.15 | 0.95 | 0.84, 1.09 | 0.47 | |
Additionally adjusting for small cell/non-small cell | 1,851 | 3,039 | 5,947 | 0.92 | 0.83, 1.03 | 0.14 | 0.92 | 0.80, 1.05 | 0.23 | |
Based upon first year after diagnosisc | 1,728 | 2,791 | 5,223 | 0.93 | 0.87, 1.05 | 0.33 | 0.99 | 0.88, 1.13 | 0.91 | |
Nested case–control analysisd,e | 2,247 | 0.93 | 0.85, 1.03 | 0.19 | 1.00 | 0.86, 1.16 | 0.97 |
Association between low-dose aspirin use before diagnosis and survival
Medication usage after diagnosis | Cancer-specific deaths | All-cause mortality | All patients | Person years | Cancer-specific mortality | All-cause mortality | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted |
P
| Adjusteda |
P
| Unadjusted |
P
| Adjusteda |
P
| |||||||||
HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | HR | 95 % CI | |||||||||
Number of patients
|
[n = 13,433]
|
[n = 13,388]
|
[n = 13,433]
|
[n = 13,388]
| ||||||||||||
Aspirin non-user | 7,577 | 8,369 | 9,564 | 9,154 | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | 1.00 | Referent | ||||
Aspirin user | 3,055 | 3,468 | 3,869 | 3,331 | 1.07 | 1.02, 1.11 | <0.01 | 1.00 | 0.95, 1.05 | 0.91 | 1.10 | 1.05, 1.14 | <0.001 | 1.01 | 0.96, 1.06 | 0.77 |
Aspirin non-user | 7,577 | 8,369 | 9,564 | 9,154 | 1.00 | Referent | 1.00 | Referent | 1.00 | 1.00 | 1.00 | Referent | ||||
Aspirin user 1 to 11 prescriptions | 2,367 | 2,690 | 2,998 | 2,608 | 1.06 | 1.01, 1.11 | 0.02 | 0.99 | 0.94, 1.04 | 0.75 | 1.09 | 1.04, 1.14 | <0.001 | 1.00 | 0.95, 1.05 | 0.90 |
Aspirin user ≥ 12 prescriptions | 688 | 778 | 871 | 723 | 1.09 | 1.01, 1.18 | 0.03 | 1.02 | 0.94, 1.11 | 0.64 | 1.11 | 1.04, 1.20 | <0.01 | 1.02 | 0.95, 1.11 | 0.57 |
Aspirin non-user | 7,577 | 8,369 | 9,564 | 9,154 | 1.00 | Referent | 1.00 | Referent | 1.00 | 1.00 | 1.00 | Referent | ||||
Aspirin user 1–365 tablets | 2,214 | 2,508 | 2,804 | 2,436 | 1.06 | 1.01, 1.12 | 0.01 | 1.00 | 0.95, 1.06 | 0.97 | 1.09 | 1.04, 1.14 | <0.001 | 1.01 | 0.96, 1.06 | 0.70 |
Aspirin user ≥366 tablets | 841 | 960 | 1,065 | 895 | 1.07 | 1.00, 1.15 | 0.06 | 0.98 | 0.91, 1.06 | 0.70 | 1.11 | 1.04, 1.18 | <0.01 | 1.00 | 0.93, 1.07 | 0.97 |
Cancer-specific deaths | All patients | Person years | Unadjusted |
P
| Adjusteda |
P
| |||
---|---|---|---|---|---|---|---|---|---|
HR | 95 % CI | HR | 95 % CI | ||||||
Main analysis: Pre-diagnostic aspirin useb | 10,632 | 13,433 | 12,485 | 1.07 | 1.02, 1.11 | <0.01 | 1.00 | 0.95, 1.05 | 0.91 |
Subgroup analyses | |||||||||
Male | 6,298 | 7,941 | 7,103 | 1.02 | 0.97, 1.08 | 0.44 | 0.98 | 0.91–1.04 | 0.46 |
Female | 4,334 | 5,492 | 5,381 | 1.13 | 1.06–1.21 | <0.001 | 1.03 | 0.95–1.11 | 0.53 |
Sensitivity analyses | |||||||||
Smoking prior to diagnosis available (and adjusted for) | 9,560 | 12,063 | 11,336 | 1.07 | 1.03–1.12 | <0.01 | 1.00 | 0.95–1.05 | 0.93 |
BMI prior to diagnosis available (and adjusted for) | 8,562 | 10,831 | 10,448 | 1.07 | 1.02–1.12 | <0.01 | 0.99 | 0.94–1.05 | 0.73 |
Aspirin use between 2 years and 6 months prior to diagnosisc | 9,746 | 12,295 | 11,418 | 1.06 | 1.01–1.11 | 0.01 | 0.99 | 0.94–1.05 | 0.76 |